Previous studies have shown that LPS and cytokines modulate the binding of glucocorticoids (GCs) in the CNS, and therefore may affect the negative feedback exerted by GCs. In this study, we investigated the effect of lipopolysaccharide (LPS) on the inhibitory action of GCs upon the adrenocortical response to a neural stressful stimulus. Male rats were treated with either LPS (50 µg/kg) or saline for 5 consecutive days. Two days later, the LPS- and saline-treated rats were injected intraperitoneally with either dexamethasone (20 µg/kg) or saline and sacrificed 3.5 h later, after exposure to acute stressful photic stimulation. In saline-pretreated rats, photic stimulation caused a 5-fold increase in serum corticosterone levels compared to basal levels, and pre-treatment with dexamethasone completely abolished this response. In LPS-pretreated rats, corticosterone levels following photic stimulation increased 20-fold, and dexamethasone was ineffective. Additional experiments were conducted to examine whether the impairment in the negative feedback was specific to the prolonged LPS treatment, rather than to LPS-induced hypersecretion of GCs. In groups of rats which were exposed to either daily acoustic stress or daily administration of corticosterone (5 mg, twice daily) for 5 days, the pattern of corticosterone secretion mimicked the corticosterone secretion induced by LPS. In these groups, the adrenocortical response to acute photic stimulation and the effect of dexamethasone were similar to saline-pretreated controls. These results suggest that LPS impairs the negative feedback of either endogenous or exogenous GC upon the adrenocortical response to stress. This finding may be relevant to the enhanced adrenocortical activity associated with sepsis and major depression.

This content is only available via PDF.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.